An international team of researchers partially funded by the EU has uncovered new information linking healthy ageing and neurodegenerative disorders including Alzheimer's disease. The research was supported in part by the CLIP project ('Mapping functional protein-RNA (ribonucleic acid) interactions to identify new targets for oligonucleotide-based therapy'), which is supported by a European Research Council (ERC) Starting Grant worth EUR 900 000 under the EU's Seventh Framework Programme (FP7). The grant runs for 5 years up to 2013. The study is presented in the journal Genome Research.

Two of the most common neurodegenerative disorders are Alzheimer's disease and frontotemporal lobar degeneration (FTLD). In this latest study, researchers led by the Medical Research Council (MRC) Laboratory of Molecular Biology in the United Kingdom probed changes in gene expression in the ageing and diseased brain, shedding new light on the biology of normal ageing and neurodegenerative illnesses.

While researchers in past studies discovered how changes in genes are read or expressed in the brain when either ageing and/or neurodegenerative diseases emerge, no one had yet directly compared, in a single study, gene expression changes in healthy ageing with those in people suffering from diseases.

For the purposes of this study, the team assessed and compared changes in gene expression linked with ageing and diseases in a region of the brain that experts say is affected in both Alzheimer's and FTLD. They compared samples from healthy subjects, aged between 16 and 102, with samples from diseased subjects. The researchers identified similar changes in gene expression patterns linked to ageing and neurodegenerative diseases.

'Surprisingly, the [diseased] samples contained the same age-related changes as healthy individuals over the age of 80,' says senior author Dr Jernej Ule of the MRC Laboratory of Molecular Biology.

Lead author Dr James Tollervey of the MRC Laboratory of Molecular Biology adds that: 'Ageing-related changes were apparent in the diseased individuals as young as 50 years, roughly 25 years before we would expect to see similar changes in healthy individuals.'

Despite striking similarities, the researchers discovered differences between gene expression in the normal ageing brain and expression in Alzheimer's and FTLD. This was especially evident in the patterns of alternative splicing, where parts of an RNA molecule are arranged differently to adjust the message, a process which can be deregulated with harmful consequences.

During the normal ageing process, genes linked to cellular metabolism were primarily affected by changes in alternative splicing. Disease-specific changes, say the researchers, were linked to neuron-specific genes.

Changes in the expression of a number of genes coding for RNA binding proteins were observed, which, the team says, may explain some of the observed alterations in splicing.

According to the researchers, this study will lead to further work on normal ageing and neurodegenerative disease. 'These findings indicate that studies of healthy ageing could help unravel the processes that lead to neurodegeneration,' Dr Ule notes.

Co-author Boris Rogelj of the MRC Centre for Neurodegeneration Research at King's College London says: 'Conversely, our findings also indicate that studies of neurodegenerative diseases might help us understand how to delay the changes that take place in healthy individuals at an advanced age.'

Researchers from Slovenia and the United States also contributed to this study.

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